Abnormalities in immunoregulatory T-lymphocyte numbers and/or function have been observed in a variety of disease states (e.g. immunodeficiency disorders, autoimmune diseases) as well as in young infants and aged individuals. The objective of this research program is to determine if the function of regulatory T-lymphocytes can be selectively modified by neurohormones or other pharmacologic agents. In preliminary studies we have found that adenosine, H1 and H2 histamine agonists altered the expression of lymphocytes surface receptors for IgG (RFc gamma) and significantly modified the behavior of T-lymphocytes subsets in their regulation of B-cell differentiation to immunoglobulin secreting plasma cells in vitro. We will attempt to determine a) the extent to which regulatory lymphocyte function can be modified by neurohormones and other pharmacologic agents and b) the immunologic and pharmacologic mechanisms by which these functional changes occur. Peripheral blood T-lymphocytes are isolated by rosetting with sheep erythrocytes (E) and fractionated into T-subsets with predominately "helper" or "suppressor" activity based upon differential sensitivity of their E receptors to theophylline or the presence of receptors for IgG (RFc gamma) or IGM (RFc mu). We will attempt to develop monoclonal hybridoma antibodies to some immunoregulatory T-subsets to facilitate isolation of these cells for study. Unfractionated T-lymphocytes and T-subsets are exposed to drug and then studied for changes in expression of lymphocyte surface characteristics (e.g. RFc gamma, RFc mu, Ia-antigen) as well as modification of their immunoregulatory activity using an in vitro assay of T-lymphocyte-dependent B-lymphocyte differentiation to immunoglobulin secreting plasma cells. The pharmacological mechanisms involved in the interactions between hormone receptors and "immunologic" receptors will be investigated by analysis of cyclic AMP receptor binding (i.e., protein kinase activation) and neurohormone-dependent protein phosphorylation.